Prevalence of comorbidity of autism and ADHD and associated characteristics in school population: EPINED study.

Autism and attention deficit hyperactivity disorder (ADHD) comorbidity in the school population have been understudied. This study estimates its prevalence considering both parents' and teachers' reports and clinical diagnosis. Sociodemographic, clinical, and cognitive data were compared by diagnostic groups: autism, ADHD, autism and ADHD, subthreshold autism spectrum disorder (ASD), subthreshold ADHD, and children without neurodevelopmental conditions. Following a two-phase design, 3727 parents and teachers (1802 preschoolers, 1925 school-age children) participated in the first phase. Subsequently, 781 participants underwent individual assessment for DSM-5 diagnoses. The estimated prevalence of the comorbid diagnosis was 0.51% (0.28%-0.74%), with significant sex differences (0.16% girls, 0.89% boys). The cooccurrence of symptoms of autism and ADHD reported by parents or teachers was 3.2% and 2.6%, respectively. ADHD comorbidity was observed in 32.8% of autistic children and 31.4% of those with subthreshold ASD. ASD comorbidity was observed in 9.8% of children with ADHD and 5.7% of those with subthreshold ADHD. Comorbidity was reported by at least one informant in 95% of children. Only 15.8% of children with autism and ADHD had been previously diagnosed with both conditions. Early detection and accurate comorbidity diagnosis are crucial to address the clinical and socio-educational needs of these children.

Cyclophosphamide-free mobilisation increases safety while preserving the efficacy of autologous haematopoietic stem cell transplantation in refractory Crohn's disease patients.

BACKGROUND AND AIM: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for refractory Crohn's disease [CD]. However, high adverse event rates related to chemotherapy toxicity and immunosuppression limit its applicability. This study aims to evaluate AHSCT's safety and efficacy using a cyclophosphamide (Cy)-free mobilisation regimen. METHODS: A prospective observational study included 14 refractory CD patients undergoing AHSCT between June 2017 and October 2022. The protocol involved outpatient mobilisation with G-CSF 12-16 µg/kg/daily for 5 days, and optional Plerixafor 240 µg/d (1-2 doses) if the CD34+ cell count target was unmet. Standard conditioning with Cy and anti-thymocyte globulin was administered. Clinical, endoscopic, and radiological assessments were conducted at baseline and during follow-up. RESULTS: All patients achieved successful outpatient mobilisation (7 patients needed Plerixafor) and underwent transplantation. Median follow-up was 106 weeks (IQR 52-348). No mobilisation-related serious adverse events (SAEs) or CD worsening occurred. Clinical and endoscopic remission rates were 71% and 41.7% at 26 weeks, 64% and 25% at 52 weeks, and 71% and 16.7% at the last follow-up. The percentage of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 14% at 26 weeks, 57% at 52 weeks, and 86% at the last follow-up. Peripheral blood cell populations and antibody levels post-AHSCT were comparable to Cy-based mobilisation. CONCLUSIONS: Cy-free mobilisation is safe and feasible in refractory CD patients undergoing AHSCT. Although relapse occurs in a significant proportion of patients, clinical and endoscopic responses are achieved upon CD-specific therapy reintroduction.

Vasoactive intestinal peptide exerts an osteoinductive effect in human mesenchymal stem cells.

Several neuropeptides present in bone tissues, produced by nerve fibers and bone cells, have been reported to play a role in regulating the fine-tuning of osteoblast and osteoclast functions to maintain bone homeostasis. This study aims to characterize the influence of the neuropeptide vasoactive intestinal peptide (VIP) on the differentiation process of human mesenchymal stem cells (MSCs) into osteoblasts and on their anabolic function. We describe the mRNA and protein expression profile of VIP and its receptors in MSCs as they differentiate into osteoblasts, suggesting the presence of an autocrine signaling pathway in these cells. Our findings reveal that VIP enhances the expression of early osteoblast markers in MSCs under osteogenic differentiation and favors both bone matrix formation and proper cytoskeletal reorganization. Finally, our data suggest that VIP could be exerting a direct modulatory role on the osteoblast to osteoclast signaling by downregulating the receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio. These results highlight the potential of VIP as an osteoinductive differentiation factor, emerging as a key molecule in the maintenance of human bone homeostasis.

Evaluation of European LeukemiaNet 2022 risk classification in patients undergoing allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: Identification of a very poor prognosis genetic group.

European LeukemiaNet refined their risk classification of acute myeloid leukaemia (AML) in 2022 (ELN 2022) according to the two new myeloid classifications published the same year. We have retrospectively assessed the prognostic value of the ELN 2022 in 120 AML patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT), including 99 in first complete response (CR1) from 2011 to 2021 in our centre. Adverse risk patients (Adv) presented inferior outcome in terms of overall survival (OS) and leukaemia-free survival (LFS) (OS [p = 0.003], LFS [p = 0.02]), confirmed in multivariate analysis (hazard ratio [HR] for OS = 2.00, p = 0.037). These results were also seen in patients allografted in CR1. Further analysis identified a subgroup named adverse-plus (AdvP), including complex karyotype, MECOM(EVI1) rearrangements and TP53 mutations, with worse outcomes than the rest of groups of patients, including the Adv (HR for OS: 3.14, p < 0.001, HR for LFS: 3.36, p < 0.001), with higher 2-year cumulative incidence of relapse (p < 0.001). Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo-HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group.

Pitahaya (Hylocereus ocamponis)-Peel and -Flesh Flour Obtained from Fruit Co-Products-Assessment of Chemical, Techno-Functional and In Vitro Antioxidant Properties.

The aim of this work was to assess the chemical composition and physico-chemical, techno-functional, and in vitro antioxidant properties of flours obtained from the peel and flesh of pitahaya (Hylocereus ocamponis) to determine their potential for use as ingredients for food enrichment. The chemical composition, including total betalains, mineral content, and polyphenolic profile, was determined. The techno-functional properties (water holding, oil holding, and swelling capacities) were also evaluated. For the antioxidant capacity, four different methodologies, namely ferrous ion-chelating ability assay, ferric-reducing antioxidant power assay; 1,1-Diphenyl-2-picrylhydrazyl radical scavenging ability assay, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical assay, were used. Pitahaya-peel flour had higher values for protein (6.72 g/100 g), ash (11.63 g/100 g), and dietary fiber 56.56 g/100 g) than pitahaya-flesh flour, with values of 6.06, 3.63, and 8.22 g/100 g for protein, ash, and dietary fiber, respectively. In the same way, pitahaya peel showed a higher content of minerals, betalains, and polyphenolic compounds than pitahaya-flesh flour, with potassium (4.43 g/100 g), catechin (25.85 mg/g), quercetin-3-rhamnoside (11.66 mg/g) and myricetrin (12.10 mg/g) as principal compounds found in the peel. Again, pitahaya-peel flour showed better techno-functional and antioxidant properties than pitahaya-flesh flour. The results obtained suggest that the flours obtained from the peel and pulp of pitahaya (H. ocamponis) constitute a potential material to be utilized as an ingredient in the food industry due to the high content of bioactive compounds such as betalains, phenolic acids, and flavonoids, with notable antioxidant capacity.

Systematic evaluation of methods for iron-impregnation of biochar and effects on arsenic in flooded soils.

There is a need for innovative strategies to decrease the mobility of metal(loids) including arsenic (As) and cadmium (Cd) in agricultural soils, including rice paddies, so as to minimize dietary exposure to these toxic elements. Iron (Fe)-modified biochars (FBCs) are used to immobilize As and Cd in soil-water systems, but there is a lack of clarity on optimal methods for preparing FBCs because there are only limited studies that directly compare BCs impregnated with Fe under different conditions. There is also a lack of information on the long-term performance of FBCs in flooded soil environments, where reductive dissolution of Fe (oxy)hydroxide phases loaded onto biochar surfaces may decrease the effectiveness of FBCs. This study uses material characterization methods including FTIR, SEM-EDX, BET, and adsorption isotherm experiments to investigate the effects of Fe-impregnation methods (pH, pyrolysis sequence, and sonication) on the morphology and mineralogy of Fe loaded onto the biochar surface, and to FBC adsorbent properties for arsenate (As(V)), arsenite (As(III)), and Cd. Acidic impregnation conditions favored the adsorption of As(III) onto amorphous Fe phases that were evenly distributed on the biochar surface, including within the biochar pore structure. The combination of sonication with acidic Fe-impregnation conditions led to the best adsorption capacities for As(V) and As(III) (4830 and 11,166 µg As g-1 biochar, respectively). Alkaline Fe-impregnation conditions led to the highest Cd adsorption capacity of 3054 µg Cd g-1 biochar, but had poor effectiveness as an As adsorbent. Amending soil with 5% (w/w) of an acid-impregnated and sonicated FBC was more effective than an alkaline-impregnated FBC or ferrihydrite in decreasing porewater As concentrations. The acid-impregnated FBC also had greater longevity, decreasing As by 54% and 56% in two flooded phases, probably due to the greater stability of Fe(III) within the biochar pore structure that may have a direct chemical bond to the biochar surface. This study demonstrates that FBCs can be designed with selectivity towards different As species or Cd and that they can maintain their effectiveness under anaerobic soil conditions. This is the first study to systematically test how impregnation conditions affect the stability of FBCs in soils under multiple drying-rewetting cycles.

Effects of CYP3A5 Genotype on Tacrolimus Pharmacokinetics and Graft-versus-Host Disease Incidence in Allogeneic Hematopoietic Stem Cell Transplantation.

Tacrolimus (Tac) is pivotal in preventing acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). It has been reported that genetic factors, including CYP3A5*3 and CYP3A4*22 polymorphisms, have an impact on Tac metabolism, dose requirement, and response to Tac. There is limited information regarding this topic in alloHSCT. The CYP3A5 genotype and a low Tac trough concentration/dose ratio (Tac C0/D ratio) can be used to identify fast metabolizers and predict the required Tac dose to achieve target concentrations earlier. We examined 62 Caucasian alloHSCT recipients with a fast metabolizer phenotype (C0/dose ratio ≤ 1.5 ng/mL/mg), assessing CYP3A5 genotypes and acute GVHD incidence. Forty-nine patients (79%) were poor metabolizers (2 copies of the variant *3 allele) and 13 (21%) were CYP3A5 expressers (CYP3A5*1/*1 or CYP3A5*1/*3 genotypes). CYP3A5 expressers had lower C0 at 48 h (3.7 vs. 6.2 ng/mL, p = 0.03) and at 7 days (8.6 vs. 11.4 ng/mL, p = 0.04) after Tac initiation, tended to take longer to reach Tac therapeutic range (11.8 vs. 8.9 days, p = 0.16), and had higher incidence of both global (92.3% vs. 38.8%, p < 0.001) and grade II-IV acute GVHD (61.5% vs. 24.5%, p = 0.008). These results support the adoption of preemptive pharmacogenetic testing to better predict individual Tac initial dose, helping to achieve the therapeutic range and reducing the risk of acute GVHD earlier.

Utility of immature platelet fraction in the Sysmex XN-1000V for the differential diagnosis of central and peripheral thrombocytopenia in dogs and cats.

BACKGROUND: The immature platelet fraction (IPF), a parameter obtained by the Sysmex XN-1000V analyzer, is used in humans to differentiate between central (CEN) and peripheral (PER) thrombocytopenia (TP) but has not been evaluated in small animals. OBJECTIVES: Compare IPF between healthy, clinical non-TP and TP dogs and cats, study IPF in different causes of TP in dogs and cats and, establish IPF reference intervals (RIs), and study the effect of age and sex on IPF in healthy dogs and cats. ANIMALS: A total of 3281 dogs and 726 cats. METHODS: Retrospective review of medical records. Animals were classified as nonthrombocytopenic (healthy group and group of clinical patients without TP [NTP]) or TP. These latter animals were subclassified as pseudothrombocytopenia (PSE), CEN and PER, based on evaluation of platelet clumps, estimated platelet count in blood smears and final diagnosis. Blood samples were evaluated using a Sysmex XN-1000V with a specific platelet channel (PLT-F). RESULTS: The IPF was significantly different between each subtype of TP in both species. Immature platelet fractions <6.9% in dogs or 13.6% in cats, once PSE has been eliminated by review of blood smears, are indicative of CEN. Reference intervals for IPF were 0.5%-8% in healthy dogs and 1%-40.3% in healthy cats. CONCLUSIONS AND CLINICAL IMPORTANCE: We determined that IPF can differentiate between CEN and PER in dogs and cats, guiding additional testing and avoiding more invasive procedures (bone marrow sampling). A blood smear always should be evaluated to rule out platelet clumping.

Increased Serum Levels of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) in Mobilized Healthy Donors with G-CSF: A Cohort Study.

Limited data regarding elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in mobilized donors with G-CSF is available. We extended these findings by examining serum NT-proBNP in a cohort study including 35 healthy donors and 69 patients who received G-CSF for CD34+ mobilization as well as 54 patients who did not receive G-CSF but who underwent collection of CD3+ cells for chimeric antigen receptor (CAR) T-cell manufacturing. No donor in the three cohorts experienced significant cardiac adverse events. NT-proBNP levels were measured before and after G-CSF administration and after finishing apheresis procedure. NT-proBNP increase was observed in mobilized healthy donors after G-CSF administration, but was not observed in mobilized or non-mobilized patients. Only in the cohort of healthy donors, pairwise comparisons using Wilcoxon signed ranks test showed a significant increase between the mean serum NT-proBNP level after G-CSF administration and the mean serum NT-proBNP level measured before G-CSF administration (231.09 ± 156.15 pg/mL vs. 58.88 ± 26.84 pg/mL; P < .01). No correlation was observed between NT-proBNP increase and G-CSF dose (rs = 0.09; n = 32; P = .6) and no other variables contributing to predict serum NT-proBNP increase were detected. In conclusion, we observed a statistically, although not clinically, significant increase of NT-proBNP in healthy donors who received G-CSF as CD34+ cell mobilization.

EASIX and cardiac adverse events after allogeneic hematopoietic cell transplantation.

This study investigates the interaction between endothelial activation, indirectly measured using EASIX, and the probability of presenting cardiac adverse events (CAE) during the first year after allo-HCT. The 437 consecutive adults undergoing PB allo-HCT from 2012 and 2021 were included. EASIX was retrospectively calculated before and during the first 6 months after allo-HCT and transformed to log2-base to conduct the statistical analysis. The median age was 53, 46 (10.5%) patients had previous history of cardiac disease, MAC allo-HCTs were performed in 186 (42.6%) patients, and PTCY was administered in 242 (55.5%). The 1-year incidence of CAE was 12.6% (n = 55). The most prevalent cardiac events were heart failure and arrhythmias, 32.7% and 23.6% respectively, and the day +100 mortality rate of these patients was 40.5%. During the first 6 months after allo-HCT, EASIX trends were significantly higher in patients who developed CAE. Regression analyses confirmed that higher log2-EASIX values were predictors for higher risk for CAE during the first year after allo-HCT. This analysis identifies a significant association between higher endothelial activation, indirectly measured using EASIX, and higher risk for cardiac toxicity diagnosed during the first year after allo-HCT and extends the applicability of EASIX for identifying patients at risk for CAE.

Hospital admission and its common causes in children on antiretroviral therapy (ART) in Lilongwe Malawi between 2001 and 2016: a retrospective cross-sectional study.

BACKGROUND: Paediatric HIV data shows a variable and sometimes catastrophic response in the initial stage of ART regimen administration. The burden of disease that affects children in their first year of treatment is not comprehensively available. OBJECTIVE: Objective of our study was to describe patterns of admission in children; before ART initiation, within the first six months, and post-six months of ART between 2001 and 2016. METHODS: Principal caregivers of 260 children (45.7% females 54.2% males, all <15 years) on ART for at least six months were interviewed about admissions of their children. Diagnoses were verified from the health passport books. Data on age, sex, date of ART initiation was obtained from the database of Baylor College of Medicine in Lilongwe. Data were analysed using Excel for descriptive analysis. Chi Square Test was used to test for significance. RESULTS: There were more admissions before starting ART 74% (95%CI 68.67-79.33%) vs. 42% (95%CI 36.00-48.00%), after starting ART (p = <0.001 at 5% significance level); after six months of ART 34% (95%CI 28.24-39.76) vs. 20% (95% CI 15.51-24.86%) (p = <0.001 at 5% significance level). The commonest causes of admission were pneumonia, malaria, tuberculosis, anaemia; no difference in causes of admission within the first and after six months of ART initiation. CONCLUSION: ART significantly reduces admission in children living with HIV. The common causes of admission are HIV non-specific conditions. No difference between causes of admission within and after six months of ART.

Aquatic Exercise in Physical Therapy Treatment for Fibromyalgia: Systematic Review.

Fibromyalgia is a chronic condition characterized by musculoskeletal pain. The aim of this study was to synthesize scientific evidence on the effects of aquatic exercise programs on pain and quality of life in individuals with fibromyalgia. This review was carried out using the following databases in January 2024: Cochrane Library, PEDro, PubMed, SCOPUS, and Web of Science. Four clinical trials focusing on aquatic exercise as a treatment for patients with fibromyalgia were selected. These trials were published in English between 2019 and 2024. Pain recorded using the Visual Analog Scale (VAS) and quality of life with the Short Form-36 Health Survey (SF-36) or Fibromyalgia Impact on Quality of Life (FIQ) were the most commonly analyzed variables. This review was carried out according to the PRISMA statement and was registered in PROSPERO (CRD42024510219). The results in terms of pain and quality of life were positive. In conclusion, these findings support the incorporation of aquatic exercise into fibromyalgia physical therapy treatment. However, the benefits could be equivalent to those of other exercise modalities, underscoring the need for individualized adaptation to each patient's needs.

The Maternal Omega-3 Long-Chain Polyunsaturated Fatty Acid Concentration in Early Pregnancy and Infant Neurodevelopment: The ECLIPSES Study.

Omega-3 Long-Chain Polyunsaturated Fatty Acids (n-3 LCPUFAs) play a key role in early neurodevelopment, but evidence from observational and clinical studies remains inconsistent. This study investigates the association between maternal n-3 LCPUFA, Docosahexaenoic Acid (DHA), and eicosapentaenoic acid (EPA) concentrations during pregnancy and infant development functioning at 40 days. This study includes 348 mother-infant pairs. Maternal serum concentrations were assessed in the first and third trimesters alongside sociodemographic, clinical, nutritional, psychological, and obstetrical data. At 40 days, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was administered. An adjusted analysis revealed that lower first-trimester n-3 LCPUFA and DHA concentrations are associated with better infant motor development. These results underscore the potential significance of the maternal n-3 LCPUFA status in early pregnancy for influencing fetal neurodevelopment. However, the complexity of these associations necessitates further investigation, emphasizing the urgent need for additional studies to comprehensively elucidate the nuanced interplay between the maternal n-3 LCPUFA status and infant neurodevelopment.

Association between of vitamin B12 status during pregnancy and probable postpartum depression: the ECLIPSES study.

BACKGROUND: B12 vitamin is essential for the functioning of the nervous system and the production of mood-related neurotransmitters. However, information on its association with postpartum depression (PPD) is limited. OBJECTIVE: To examine the effect of serum vitamin B12 levels during pregnancy on PPD, in healthy pregnant women from the Mediterranean region of Catalonia, Spain. METHOD: This longitudinal study included a subsample of women at 54 days (7.7 weeks) postpartum (n = 336), who participated in the ECLIPSES Study conducted out in Tarragona, Spain. Maternal concentrations of vitamin B12 were determined in the first and third trimester of pregnancy and sociodemographic, nutritional, and psychological data were collected. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: The prevalence of probable PPD was 21%. After adjusting for sociodemographic, lifestyle, biochemical parameters, and postpartum characteristics the regression model showed a negative association between EPDS scores and the highest quartile of serum vitamin B12 (first quartile (reference) vs. fourth quartile), (ß = -1.267, 95% CI = -2.461, -0.073, p = 0.038). CONCLUSION: Maintaining a normal-high level of vitamin B12 during early pregnancy can contributes to preventing PPD.

Enamel fluorosis related with fluoride-containing water ingestion and urinary excretion in schoolchildren.

Background: Natural water sources are considered as the major environmental exposure of fluoride, resulting in increased prevalence of enamel fluorosis. This type of natural exposure should be permanently monitored to avoid the interactions with other non-natural fluoride sources. We evaluated the prevalence of enamel fluorosis in Colombian schoolchildren and its relationship with fluoride-containing water ingestion exposure dose and urinary fluoride excretion. Material and Methods: We included 923 schoolchildren aged 7-12 years residing in eight municipalities in Colombia. Sampling of consumption water was performed in major aquifers used for daily supply. Samples were collected in 98 polyethylene containers and refrigerated until analysis. Water and urine fluoride concentrations were measured using the fluoride selective electrode method. Enamel fluorosis was evaluated using Thylstrup and Ferjerskov Index (TFI). Demographic and anthropometric characteristics were assessed. Besides, other exposures to non-natural fluoride were also evaluated. Logistic regression was applied for multiple analyses. Results: The median fluoride concentration in water and urine samples was 10.5 mg/L and 0.63 mg/L respectively, with the highest value found in Algarrobo-Magdalena, and the lowest value found in Manzanares-Caldas. The overall prevalence of enamel fluorosis was 86.1%, being more frequent the mild codes with TFI-1 to TFI-2. The highest prevalence was found in Margarita-Bolívar and Manzanares-Caldas, and the most severe codes (TFI-5 to TFI-9) were detected in Manzanares-Caldas. The multiple analysis revealed water ingestion exposure dose, urinary excretion, involuntary intake of toothpaste, amount of table salt consumption and sex as significant factors (p< 0.001). Conclusions: The fluoride ingestion exposure dose and its subsequent urinary excretion could be used as estimators of past fluoride exposure, explaining the current prevalence of enamel fluorosis in Colombian schoolchildren. Key words:Fluoride, groundwater ingestion, enamel fluorosis, prevalence, severity.

Total mercury and selenium levels in commercial shrimp along the Pacific coast of Mexico.

The present study analyzed the content of total mercury (THg) and selenium (Se) in the muscle of shrimp collected from local markets in the 11 Pacific coastal states of Mexico. Methylmercury (MeHg) concentration, Se:Hg ratio, health benefits value from selenium consumption (HBVSe) and the permissible weekly consumption were estimated to assess the health risk to consumers. All THg and Se concentrations were below the maximum permissible limits. All hazard quotient (HQ) values were <1, however in Hermosillo, Culiacán and Guadalajara, the Se:Hg ratio and HBVSe were <1 and negative, due to the low concentrations of Se. As a general conclusion, there is no risk nor benefit from the consumption of shrimp from the Pacific coast of Mexico due to its Hg and Se content.

Chemical multiscale robotics for bacterial biofilm treatment.

A biofilm constitutes a bacterial community encased in a sticky matrix of extracellular polymeric substances. These intricate microbial communities adhere to various host surfaces such as hard and soft tissues as well as indwelling medical devices. These microbial aggregates form a robust matrix of extracellular polymeric substances (EPSs), leading to the majority of human infections. Such infections tend to exhibit high resistance to treatment, often progressing into chronic states. The matrix of EPS protects bacteria from a hostile environment and prevents the penetration of antibacterial agents. Modern robots at nano, micro, and millimeter scales are highly attractive candidates for biomedical applications due to their diverse functionalities, such as navigating in confined spaces and targeted multitasking. In this tutorial review, we describe key milestones in the strategies developed for the removal and eradication of biofilms using robots of different sizes and shapes. It can be seen that robots at different scales are useful and effective tools for treating bacterial biofilms, thus preventing persistent infections, the loss of costly implanted medical devices, and additional costs associated with hospitalization and therapies.